{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T21:37:31Z","timestamp":1793223451407,"version":"4.5.0"},"reference-count":38,"publisher":"European Respiratory Society (ERS)","issue":"1","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2024,8,29]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Bronchiectasis is characterised by uncontrolled neutrophil serine protease (NSP) activity. Cathepsin C (CatC; dipeptidyl peptidase 1) activates NSPs during neutrophil maturation. CatC inhibitors can potentially reduce neutrophil-mediated lung damage. This phase II, randomised, double-blind, placebo-controlled trial (AIRLEAF<jats:sup>\u00ae<\/jats:sup>; clinicaltrials.gov identifier<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05238675\">NCT05238675<\/jats:ext-link>) evaluated efficacy, safety and optimal dosing of BI 1291583, a novel, reversible CatC inhibitor, in adults with bronchiectasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In total, 322 participants were randomised (2:1:1:2) to receive one of three oral doses of BI 1291583 (1\u2005mg\/2.5\u2005mg\/5\u2005mg) or placebo for 24\u201348\u2005weeks. A multiple comparison procedure and modelling approach was used to demonstrate a nonflat dose\u2013response curve based on the time to first pulmonary exacerbation up to week 48. In addition, efficacy of individual BI 1291583 doses was evaluated based on the frequency of exacerbations, severe exacerbations (fatal or leading to hospitalisation and\/or intravenous antibiotic administration), lung function and quality of life.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A significant dose-dependent benefit of BI 1291583 over placebo was established based on time to first exacerbation (shape: maximum effect curve 1; adjusted p=0.0448). Treatment with BI 1291583 5\u2005mg and 2.5\u2005mg numerically reduced the risk of an exacerbation compared with placebo (hazard ratio (95% CI) 0.71 (0.48 to 1.05) and 0.66 (0.40 to 1.08), respectively; both p&gt;0.05). BI 1291583 2.5\u2005mg showed numerically better efficacy compared with 5\u2005mg across several end-points; 1\u2005mg was similar to placebo. The safety profile of BI 1291583 was similar to placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Treatment with BI 1291583 resulted in a reduction in the risk of experiencing an exacerbation in adults with bronchiectasis.<\/jats:p><\/jats:sec>","DOI":"10.1183\/13993003.01551-2024","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T11:07:56Z","timestamp":1725966476000},"page":"2401551","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":96,"title":["Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF, a phase II randomised, double-blind, placebo-controlled, dose-finding study"],"prefix":"10.1183","volume":"65","author":[{"given":"James 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